(±)-SLV 319
(Synonyms: (±)-SLV319; (±)-BMS-646256) 目录号 : GC10907
A selective antagonist of CB1
Cas No.:362519-49-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Rats: SLV319, rimonabant and rosiglitazone are suspended in a 10% dimethylacetamide, 10% cremophor, 10% ethanol and 70% water vehicle. Drugs are administered by oral gavage in a volume of 2 mL/kg body weight at 09:00 hours every day. Treatment groups are as follows: (i) Vehicle: ad libitum access to food (vehicle), (ii) Vehicle: restricted access to food (20% less than average food intake of ad libitum vehicle-treated group for the first 3 days of the study, then 10% less than the average food intake of the ad libitum vehicle-treated group for the remainder of the study) (restricted), (iii) Rosiglitazone (4 mg/kg), (iv) Rimonabant (3 mg/kg) (RIM 3 mg/kg), (v) Rimonabant (10 mg/kg) (RIM 10 mg/kg), (vi) (±)-Ibipinabant ((±)-SLV319) (3 mg/kg) (IBI 3 mg/kg) and (vii) Ibipinabant (10 mg/kg) (IBI 10 mg/kg). Rosiglitazone is used as a positive control for its ability to delay β-cell decline, and rimonabant is used as a positive control for CB1 antagonism[3]. |
References: [1]. Chorvat RJ, et al. JD-5006 and JD-5037: peripherally restricted (PR) cannabinoid-1 receptor blockers related to SLV-319 (Ibipinabant) as metabolic disorder therapeutics devoid of CNS liabilities. Bioorg Med Chem Lett. 2012 Oct 1;22(19):6173-80. | |
SLV 319 is described here instead of (±)-SLV 319. SLV 319, also called ibipinabant, is a CB1 antagonist with an IC50 value of 22 nM [1, 2].
There are 2 types of cannabinoid receptors (CB1 and CB2). Their endogenous ligands are primarily anandamide and 2-AG. Cannabinoid receptors and their endogenous ligands together are prominent in the control of food intake and energy metabolism. Stimulation of this endocannabinoid system triggers metabolic processes and leads to lipogenesis, weight gain, insulin resistance, dyslipidemias and impaired glucose homeostasis [2].
C2C12 murine myoblasts were model cells. Exposure to increasing concentrations of ibipinabant at the highest concentration tested (100 μM) for 24 hours significantly decreased cell viability to 73 ± 5%. After 48 hours of exposure to the drug at this concentration only 33 ± 4% of cells remained viable. Cellular reactive oxygen species (ROS) generation is an index of mitochondrial function. A more than 2-fold increase in cellular ROS generation could already be observed after 8 hours exposure to ibipinabant at a concentration of 100 μM compared to the vehicle treated C2C12 myoblasts [3].
CB1 receptor occupancy was related to potencies to increase dopamine (DA) and norepinephrine (NE) releases. In the medial prefrontal cortex (mPFC), SLV 319 caused a significant increase in the extracellular DA level at 10 mg/kg. The time course of the effects of SLV 319 and SR141716A at the 10-mg/kg dose appeared to be similar with peak effects at 30 and 180 min. But SLV 319 showed a more pronounced biphasic effect on DA release. SLV319 administration caused significant increases in extracellular concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), metabolites of DA and NE, after the 10-mg/kg dose in rat [4].
References:
[1]. Srivastava BK, Soni R, Joharapurkar A, et al. Bioisosteric replacement of dihydropyrazole of 4S-(-)-3-(4-chlorophenyl)-N-methyl-N’-[(4-chlorophenyl)-
sulfonyl]-4-phenyl-4,5-dihydro-1H-pyrazole-1-caboxamidine (SLV-319) a potent CB1 receptor antagonist by imidazole and oxazole. Bioorganic & medicinal chemistry letters, 2008, 18(3): 963-968.
[2]. Chorvat RJ, Berbaum J, Seriacki K, et al. JD-5006 and JD-5037: peripherally restricted (PR) cannabinoid-1 receptor blockers related to SLV-319 (Ibipinabant) as metabolic disorder therapeutics devoid of CNS liabilities. Bioorganic & medicinal chemistry letters, 2012, 22(19): 6173-6180.
[3]. Schirris TJJ, Ritschel T, Renkema GH, et al. Mitochondrial ADP/ATP exchange inhibition: a novel off-target mechanism underlying ibipinabant-induced myotoxicity. Scientific reports, 2015, 5.
[4]. Need AB, Davis RJ, Alexander-Chacko JT, et al. The relationship of in vivo central CB1 receptor occupancy to changes in cortical monoamine release and feeding elicited by CB1 receptor antagonists in rats. Psychopharmacology, 2006, 184(1): 26-35.
| Cas No. | 362519-49-1 | SDF | |
| 别名 | (±)-SLV319; (±)-BMS-646256 | ||
| 化学名 | (S,E)-3-(4-chlorophenyl)-N-((4-chlorophenyl)sulfonyl)-N'-methyl-4-phenyl-4,5-dihydro-1H-pyrazole-1-carboximidamide | ||
| Canonical SMILES | ClC1=CC=C(C=C1)C2=NN(/C(NS(=O)(C(C=C3)=CC=C3Cl)=O)=N\C)C[C@@H]2C4=CC=CC=C4 | ||
| 分子式 | C23H20Cl2N4O2S | 分子量 | 487.4 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 30 mg/ml,Ethanol:PBS (pH 7.2) (1:2): 0.25 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0517 mL | 10.2585 mL | 20.517 mL |
| 5 mM | 0.4103 mL | 2.0517 mL | 4.1034 mL |
| 10 mM | 0.2052 mL | 1.0259 mL | 2.0517 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。